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19 Cards in this Set
- Front
- Back
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How was the TRP channel discovered? |
Initially discovered as a channel responsible for hyperpolarizing current in fly eyes in response to light (stronger current if in dark for longer time beforehand). Not responsible for immediate downstroke of current, but responsible for the longer, sustained part of it |
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Fun fact |
TRP channels didn't get cool until they found out they responded to spiciness |
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What is the general structure of the TRP channels? |
6 TM domains (pore loop between S5 and S6) with a large N-terminal cytosolic domain containing anchor repeat domains. Also rather large C-terminal cytosolic domain |
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What does it mean that a channel is polymodal? |
This means it's activated by different types of stimuli (like temp and chemicals) |
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What are the TRP channels responsible for sensing heat? Cold?
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TRPV3 is activated in response to warmth (like 30 deg?), then TRPV1 is activated at about 45 degrees, then TRPV2 at 50. TRPM8 is the minty one activated at 15 degrees then really cold TRPA1 is activated at 5 degrees and by wasabi |
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How would one go about determining the temp sensitive region of an ion channel? |
Selectively mutating different regions until temp sensitivity (but not other sensitivities) dissapear |
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What are the three proposed mechanism for temperature sensation in a channel? |
A temperature sensitive AA sequence undergoes conformational change resulting directly from temp change and opens the channel, heat changes membrane viscosity, and heat will cause second messenger activity which opens the channel. |
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How could you test for the membrane bilayer theory of temp sensation? |
Purify protein and put it into an artificial membrane. Then vary the viscosity chemically without changing temperature and see if activity changes. |
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Fun fact |
There is a channel that hyperpolarizes in response to temp change called TRK1 |
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What is the function of anchor repeat domains in TRPV4 channels? |
They are domains that can be anchored to either cytoskeleton or lipid membranes. This means that it can be in direct contact with the inner face of the PM and mechanosensitive. As a result, TRPV4 channels open in response to a hypotonic solution |
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What kind of ions are conducted by the TRP channels? |
Non-selectively, cations |
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T or F; TRP channels tend to be voltage sensitive |
False, they are voltage independent |
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Why is it that if a huge amount of calcium is added to the extracellular solution, your TRP channels will stop conducting any current inward? |
The anomolous mole fraction effect (TRP channels, like most non-selective cation channels actually like sodium better, so if there is too much calcium, the sodium will block the pore). |
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If a certain channel causes increased intracellular calcium levels where could this calcium come from? How would you test for this? |
It could be influx from the extracellular solution or release from the ER. You'd test this by either using a calcium free wash solution to see if the current disappears or add a calcium chelator to remove extracellular calcium |
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Physiologically, what are the known functions of TRPV4? |
It is in the hypothalamus to sense hydration, also in the bladder to sense distention. If you KO it there will also be impaired osteoclast differentiation. Further, its been shown that TRPV4 has a role in vasodilation (induce NO?) |
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Why is it that all of the physiological roles of a protein can't necessarily be found by KOs? |
Because the body is adaptable and will try to compensate for the lack of things as much as possible. |
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So if TRPV4 lack of function is involved in high blood pressure, then why isn't an agonist used as a drug? |
Because overfunction of this channel has alot of issues too |
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Important |
Different mutations in many channels (TPRV4 included) results in a huge host of different phenotypes. Just because same protein mutated doesn't mean same results. |
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What would you expect to happen if you mutate the anchor repeat domains in TRPV4? How many are there? |
6 ARDs, many things may happen including no more osmosensation, but an important thing that could happen is that the interaction with PIP2 is lost. TRPV4 is especially inhibited by PIP2 binding to its ARD (sort of inhibitedd by other PIPs too). When the mutation happens you have increased TRPV4 channel function, which causes progressive neuropathy (neuronal death due to calcium toxicity cuz channel opens too much). |
